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A synonymous variation in protease-activated receptor-2 is associated with atopy in Korean children

 Ji Hyun Lee  ;  Kyung Won Kim  ;  Heon Yung Gee  ;  Jaechun Lee  ;  Keun-Hwa Lee  ;  Hae-Sim Park  ;  Seung-Hyun Kim  ;  So Won Kim  ;  Mi Na Kim  ;  Kyu-Earn Kim  ;  Kyung Hwan Kim  ;  Min Goo Lee  ;  Myung Hyun Sohn 
 JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol.128(6) : 1326-1334.e3, 2011 
Journal Title
Issue Date
Asian Continental Ancestry Group/genetics ; Base Sequence ; Blotting, Western ; Case-Control Studies ; Child ; Female ; Gene Expression ; Gene Expression Profiling ; Gene Expression Regulation/genetics* ; Genetic Predisposition to Disease/genetics* ; Genome-Wide Association Study ; Genotype ; Humans ; Hypersensitivity, Immediate/genetics* ; Immunoglobulin E/blood ; Immunoglobulin E/genetics ; Korea ; Male ; Molecular Sequence Data ; Phenotype ; Polymorphism, Single Nucleotide ; Protein Structure, Secondary ; RNA Stability ; Real-Time Polymerase Chain Reaction ; Receptor, PAR-2/chemistry ; Receptor, PAR-2/genetics* ; Reverse Transcriptase Polymerase Chain Reaction
Protease-activated receptor-2 ; SNP ; association study ; atopy ; mRNA stability
BACKGROUND: Atopic diseases are the most common chronic diseases of childhood, and the genetics of atopy are complex and heterogeneous. Protease-activated receptor-2 (PAR-2) is involved in various inflammatory diseases, but the association of PAR-2 with allergic diseases remains unclear.

OBJECTIVE: To examine the contribution of genetic variation of PAR-2 to atopic phenotypes in the Korean childhood cohort.

METHODS: We identified PAR-2 variations in a Korean population and conducted association analyses by using 316 unrelated atopic and 210 nonatopic subjects. We analyzed serum IgE and total eosinophil count levels and examined PAR-2 mRNA and protein expression levels.

RESULTS: In the case-control association analysis, atopy was significantly associated with a single c.621C>T (p.I207I, rs631465) polymorphism of PAR-2 (P = .001, odds ratio = 1.95). Subjects with the c.621T risk allele had significantly higher serum IgE (P = .004) and total eosinophil count (P = .03) levels. Moreover, the positive association of c.621T was reproduced in the replication study (P = .01, joint P value of the replication < .001). An in silico analysis of RNA secondary structure prediction revealed that the C to T conversion at c.621 greatly increased predicted PAR-2 mRNA stability. This was also confirmed by an in vitro assay for mRNA stability. Furthermore, following an in vivo approach on gene expression in PBMCs showed that the expression levels of PAR-2 mRNA and protein in subjects with the c.621CT or TT genotype were significantly higher than in those with the c.621CC genotype.

CONCLUSIONS: These results indicate that the synonymous c.621C>T polymorphism in PAR-2 might be associated with the risk of atopy, potentially by altering PAR-2 gene expression.
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Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Won(김경원) ORCID logo https://orcid.org/0000-0003-4529-6135
Kim, Kyung Hwan(김경환)
Kim, Kyu Earn(김규언)
Kim, Mina(김미나) ORCID logo https://orcid.org/0000-0002-1675-0688
Kim, So Won(김소원)
Sohn, Myung Hyun(손명현) ORCID logo https://orcid.org/0000-0002-2478-487X
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
Lee, Ji Hyun(이지현)
Gee, Heon Yung(지헌영) ORCID logo https://orcid.org/0000-0002-8741-6177
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